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is considered a soluble compound, it does not contain
either polyethylene glycol or benzyl alcohol, and there
are recommendations for its use when a nonparticulate
corticosteroid is indicated.2,22,23,27
- Dexamethasone. Preservative-free dexamethasone
(eg, Decadron phosphate) is freely soluble, does not
contain either polyethylene glycol or benzyl alcohol,
and is considered a nonparticulate corticosteroid with
minimal particle aggregation.2,22,23,27 It has not been asso-
ciated with major neurologic complications and appears
to have a better safety profile compared with other
corticosteroids used for epidural injections. Preservative-
free dexamethasone is reported to be long-acting with
minimal mineralocorticoid activity. It has increased
glucocorticoid activity, so increased blood glucose levels
are possible. Concerns regarding equipotency and ef-
fectiveness of using only a nonparticulate steroid in
a population of patients with chronic pain have been
voiced. In theory, soluble nonparticulate corticosteroids
are washed out of their targeted region more readily.
They may not reduce the inflammation and produce the
long-term relief that one might expect with an insoluble
particulate steroid.^22 However, investigations comparing
triamcinolone with dexamethasone for major joint injec-
tions have demonstrated no statistically significant dif-
ference between onset, duration, or efficacy.^22 In 2013,
dexamethasone was demonstrated to be noninferior to
the particulate steroids when the investigators compared
pain relief and functional improvement at 2 months,
and when they accounted for potency equivalence.^37 In
2015, an expert panel from 13 national specialty stake-
holder societies agreed that the nonparticulate steroid
dexamethasone should be used for the initial injection
in lumbar TF epidural injections but may be followed
with particulate steroids for subsequent injections, even
if initial injection therapy failed.^13
Discussion
Many investigations have evaluated the size and ag-
gregation of corticosteroids while comparing the effec-
tiveness of particulate vs nonparticulate solutions. In
2007, Benzon and colleagues^27 compared the particles of
methylprednisolone, triamcinolone, betamethasone, and
dexamethasone in both diluted and undiluted samples.
At that time, they did not recommend the routine use of
dexamethasone without further study of its safety and
efficacy. However, they did recommend commercially
prepared betamethasone when an insoluble steroid is
preferred.^27 In 2008, Derby and colleagues^26 evaluated
particulate size and aggregation of 4 types of corticoste-
roid preparations: dexamethasone sodium phosphate,
triamcinolone acetonide, betamethasone sodium phos-
phate, and methylprednisolone acetate. The dexametha-
sone sodium phosphate particle size was approximately
10 times smaller than the red blood cells, and the
particles did not appear to aggregate. Dexamethasone
sodium phosphate had the lowest density, which would
significantly reduce the risk and prevent embolic infarcts
after an intra-arterial injection. The authors concluded
that spine interventionalists should consider using dexa-
methasone when performing ESIs.^26
Results from investigations are mixed regarding the
comparative effectiveness of particulate vs nonparticu-
late corticosteroids. Traditional belief is that particulate
steroid solutions when administered in the epidural
space, using appropriate and accepted techniques, will
provide longer durations of pain relief compared with the
nonparticulate solution. Interestingly, most early investi-
gations that established the efficacy of the ESI primarily
used particulate corticosteroids. It is generally accepted
these studies had methodologic problems.13,22 There are
many challenges with appropriate scientific evaluation of
the evidence regarding ESIs. Knowledge and technology
regarding interventional strategies continue to advance
at a rapid rate. Findings from investigations 10 years ago
may no longer be considered fair comparisons in 2018.
Results of more recent investigations suggest that the
comparative effectiveness of dexamethasone compared
with particulate steroids may not be as great as previously
believed. In 2013, a retrospective observational study that
included a noninferiority analysis of dexamethasone rela-
tive to particulate steroids demonstrated no evidence of
decreased effectiveness in lumbar TF ESIs performed for
radicular pain with or without radiculopathy.^37 In 2014, a
prospective randomized double-blind trial was conducted
to evaluate the differences in effectiveness between partic-
ulate and nonparticulate corticosteroids for acute radicu-
lar pain due to lumbar disk herniation.^11 The investigators
concluded that epidural corticosteroid injections are an
effective treatment of acute radicular pain associated with
disk herniation, and pain symptoms improved with only
1 or 2 injections. Dexamethasone appeared to possess
reasonably similar effectiveness but did require slightly
more injections to achieve the same outcomes. Slightly
more than 17% of the dexamethasone group received 3
injections vs 2.7% of the triamcinolone group.^11
There are no corticosteroids currently approved by the
US Food and Drug Administration (FDA) for injection
into the epidural space of the spine. The FDA provides
a warning that epidural injection of corticosteroids may
result in rare but serious adverse events, including loss
of vision, stroke, paralysis, and death, necessitating the
addition of a warning label for injectable corticoste-
roids.12,13 As a result of collaboration between the FDA
and selected specialty stakeholders, safeguards were
developed to prevent neurologic complications after ESI.
The unanimous consensus opinion is that ESIs are safe
and should be performed with image guidance using all
necessary safety precautions. Readers are encouraged to
review “Safeguards to Prevent Neurologic Complications